• Inhaled Levofloxacin Beneficial in CF Patients with Pseudomonas aeruginosa Infection
• Evaluation, Treatment, and Prevention of Vitamin D Deficiency
• Evaluation, Treatment, and Prevention of Vitamin D Deficiency in Infants and Children
• Which Treatment Is Most Cost-Effective for Heavy Menstrual Bleeding?
• ACOG Recommends Against Routine Vitamin D Screening in Pregnant Women
• FDA Approves Ointment for Chronic Anal Fissure Pain
• Junk Food Fight: Should Ads Stop Targeting Teens?
• Be Vigilant for New-Onset Diabetes with High-Dose Statins, Meta-Analysis Suggests
• Triglycerides and Cardiovascular Disease: The Experts Speak
• FDA: Silicone Breast Implants Not 'Lifetime Devices'
• Dogs Can Smell Cancer
• Double CT Scans: Often Ordered, Rarely Needed
• Retroviral Etiology for Chronic Fatigue Syndrome Questioned
• Fish Oil vs. Postpartum Depression
• Bisphosphonate-Related Jaw Osteonecrosis — Back on the Radar Screen
• Even Short-Term NSAID Use Associated with Cardiovascular Events
• High-Selenium Yeast Supplements Improve Plasma Lipid Levels
• High-Selenium Yeast Supplementation Doesn't Lower Plasma Lipid Levels
• Simvastatin plus Ezetimibe Improves Cardiovascular Outcomes in Patients
with Chronic Kidney Disease
• Playing Video Games Increases Caloric Intake
MM: This is great news for patients with CF. What makes it even more special is that Levofloxacin will very soon be available in the generic form & possibly the pure raw drug so this product may be provided by compounding pharmacists almost immediately with a prescription.
Am J Respir Crit Care Med 2011 Jun 1; 183:1510
Inhaled Levofloxacin Beneficial in CF Patients with
Pseudomonas aeruginosa Infection
In a placebo-controlled trial, inhaled levofloxacin (240 mg twice daily) significantlyreduced sputum P. aeruginosa density and improved pulmonary function.
Among patients with cystic fibrosis (CF), chronic infection with Pseudomonas aeruginosa (PA) is associated with a more rapid clinical decline. Delivering antibiotics by aerosol can yield high pulmonary concentrations while limiting systemic exposure. In a manufacturer-supported, multicenter trial, researchers assessed the efficacy, safety, and tolerability of MP-376, an aerosolized formulation of levofloxacin that has activity against PA and is not inactivated in CF sputum.
A total of 151 adult CF patients with chronic PA infection were randomized to receive a 28-day course of either inhaled placebo or MP-376 at one of three dosing regimens (120 mg daily, 240 mg daily, or 240 mg twice daily). At baseline, 62% of the PA isolates were resistant to levofloxacin (minimum inhibitory concentration, >2µg/mL).
At 28 days, mean sputum PA density was increased in participants receiving placebo but was reduced in participants taking MP-376 (placebo, +0.23 log cfu/g; MP-376 240 mg twice daily, –0.73 log cfu/g; P=0.001). Mean values for forced expiratory volume in 1 second decreased in placebo recipients but improved with increasing doses of MP-376 (placebo, –2.36%; MP-376 240 mg twice daily, +6.25%; P=0.003). MP-376 was also associated with a significant reduction in need for other antipseudomonal antimicrobials. Except for taste problems with MP-376, the incidence of adverse events was similar between MP-376 and placebo.
Comment: Even though many of the PA strains were levofloxacin resistant, inhaled therapy was associated with both microbiological reduction and physiological improvement. The relatively short inhalation time (4–6 minutes for a 240-mg dose) suggests that patients might use MP-376 more regularly than older therapies, such as tobramycin.
— Neil M. Ampel, MD Published in Journal Watch Infectious Diseases June 22, 2011
Citation(s):Geller DE et al. Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa. Am J Respir Crit Care Med 2011 Jun 1; 183:1510.
http://www.ncbi.nlm.nih.gov/pubmed/21471106?dopt=Abstract
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J Clin Endocrinol Metab 2011 Jun 6
Evaluation, Treatment, and Prevention of Vitamin D Deficiency
A new practice guideline recommends against routinely measuring serum
vitamin D levels in adults.
The Endocrine Society has published a new practice guideline on vitamin D deficiency. This summary covers portions of the guideline that are relevant to adult medicine (the pediatric portion is covered elsewhere; JW Gen Med Jun 23 2011). Key points follow:
- Population-wide screening for vitamin D deficiency is not recommended because evidence to support this practice is lacking. However, screening is recommended in adults who are at high risk for deficiency, including those with osteoporosis, obesity, or history of falls.
- Vitamin D deficiency is defined as serum 25-hydroxyvitamin D (25[OH]D) level <20 ng/mL (50 nmol/L); however, serum assays are notoriously variable.
- Recommended dietary intake for adults is at least 600 IU daily (800 IU for those aged >70); however, some at-risk adults might require ≥1500 IU. Few foods contain substantial vitamin D naturally, and many adults eat little vitamin D–fortified food and do not get enough sun exposure to maintain vitamin D sufficiency. Blacks and other dark-skinned people are at higher risk for deficiency than whites.
- Both vitamin D2 (ergocalciferol) and D3 (cholecalciferol) are acceptable as supplements.
- Treatment of vitamin D deficiency is indicated mainly for skeletal reasons; evidence also suggests that treatment lowers the incidence of falls in older adults. In contrast, evidence that treatment prevents cardiovascular disease, lowers mortality, or generally improves quality of life is lacking.
Comment: Because many clinicians routinely check vitamin D levels these days, the guideline's rejection of population-wide screening is perhaps the key point for clinicians. Unfortunately, for average-risk adults, the guideline doesn't explicitly say whether clinicians should recommend daily supplements (600–800 IU) universally or should evaluate, case-by-case, whether a given person's sun exposure and dietary intake likely ensure sufficient vitamin D.
— Allan S. Brett, MD Published in Journal Watch General Medicine June 23, 2011
Citation(s):Holick MF et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011 Jun 6; [e-pub ahead of print]. (http://dx.doi.org/10.1210/jc.2011-0385)
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J Clin Endocrinol Metab 2011 Jun 6;
Evaluation, Treatment, and Prevention of Vitamin D Deficiency in
Infants and Children
Risk factors in children include breast-feeding without vitamin D supplementation, dark skin pigmentation, and maternal vitamin D deficiency.
The Endocrine Society has published a new practice guideline on vitamin D deficiency. This summary covers key points of the guideline relevant to children (the adult portion can be found at JW Gen Med Jun 23 2011).
- Screening for vitamin D deficiency is recommended only for high-risk individuals. However, risk in the pediatric population is poorly defined. Risk factors for vitamin D deficiency in children include breast-feeding without vitamin D supplementation, dark skin pigmentation, and maternal vitamin D deficiency.
- Vitamin D deficiency is defined as serum 25-hydroxyvitamin D (25[OH]D) level <20 ng/mL (50 nmol/L).This definition is consistent with the Institute of Medicine report.
- Infants (age range, 1–12 months) require at least 400 IU/day of vitamin D.
- Children (age range, 1–18 years) require 600 IU/day of vitamin D.
- Infants and children who are vitamin D–deficient should receive 2000 IU/day of vitamin D2 or vitamin D3, or 50,000 IU of vitamin D2 or vitamin D3 once weekly for 6 weeks.
Comment: Despite the plethora of recent publications on vitamin D and the apparent association between vitamin D deficiency and many diseases, the only fundamental change in vitamin D recommendations in the pediatric population has been an increase in the requirement from 400 IU to 600 IU in children older than 1 year. Population-wide screening for vitamin D deficiency is not recommended.
— Howard Bauchner, MD Published in Journal Watch General Medicine June 23, 2011
Citation(s):Holick MF et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011 Jun 6; [e-pub ahead of print]. (http://dx.doi.org/10.1210/jc.2011-0385)
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MM: This one just makes me mad. Sure, if you chop off a person’s head, they won’t have the sniffles. The idea that a hysterectomy is the most “cost-effective” treatment for excessive bleeding is no less ludicrous. What about dietary/lifestyle changes, HCG and weight loss, Bio-identical Progesterone? These are all options that were not even considered in this study. Just because a study is peer-reviewed and published, does not mean that its conclusions make any sense.
BMJ 2011 Apr 26; 342:d2202
Which Treatment Is Most Cost-Effective for Heavy Menstrual Bleeding?
An evidence-based model suggests that hysterectomy is still worth considering as a first-line approach.
Heavy menstrual bleeding can adversely affect health and quality of life. In a randomized controlled trial, initial treatment of heavy menstrual bleeding with the levonorgestrel-releasing intrauterine system (LNG-IUS) was more cost-effective than immediate hysterectomy, even though 40% of women in the LNG-IUS arm eventually underwent hysterectomies (JW Womens Health Jun 9 2004). Now, investigators have developed a Markov model to assess relative costs and effectiveness of initial treatment with the LNG-IUS, hysterectomy, or endometrial ablation.
Analysis based on the model showed that hysterectomy is the most cost-effective initial approach, when the assumption is made that all women who experience treatment failure after first-line use of the LNG-IUS subsequently would choose endometrial ablation over hysterectomy.
Comment: This analysis does not take into account the costs associated with 6 to 8 weeks' convalescence after hysterectomy, or any of the long-term complications of hysterectomy such as stress incontinence. The development of less-expensive versions of the LNG-IUS probably would shift cost-effectiveness ratios toward this option. In the meantime, for women who continue to experience heavy menstrual bleeding despite use of an LNG-IUS, cost-effectiveness ratios might be improved when hysterectomy rather than ablative therapy is chosen next.
— Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health June 2, 2011
Citation(s):Roberts TE et al. Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding: Cost effectiveness analysis. BMJ 2011 Apr 26; 342:d2202.
(http://dx.doi.org/10.1136/bmj.d2202)
http://www.ncbi.nlm.nih.gov/pubmed/21521730?dopt=Abstract
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ACOG Recommends Against Routine Vitamin D Screening in Pregnant Women
There is not enough evidence to recommend screening all pregnant women for vitamin D deficiency, according to the American College of Obstetricians and Gynecologists. (Recently, the Endocrine Society recommended screening for deficiency in high-risk individuals, including pregnant women.)
Testing maternal serum 25-hydroxyvitamin D levels may be appropriate in pregnant women who are at high risk for low vitamin D levels (e.g., vegetarians, women with limited sun exposure, and ethnic minorities with darker skin), ACOG reports in Obstetrics & Gynecology.
There is no consensus on the optimal serum level of vitamin D during pregnancy. For women who are deemed deficient in the vitamin, ACOG says that daily supplementation with 1000 to 2000 IU is safe.
http://journals.lww.com/greenjournal/Citation/2011/07000/Committee_
Opinion_No__495__Vitamin_D__Screening.32.aspx
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FDA Approves Ointment for Chronic Anal Fissure Pain
The FDA has approved nitroglycerin ointment 0.4% (Rectiv) for the treatment of moderate to severe pain associated with chronic anal fissures; a preparation that has been compounded for many years. This ointment will be the only FDA-approved prescription product for patients with this condition, according to the company.
https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cDovL3d3dy5tZWRzY2Fw
ZS5jb20vdmlld2FydGljbGUvNzQ1MTE4&ac=401
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Junk Food Fight: Should Ads Stop Targeting Teens?
The government says junk food marketers shouldn't advertise to kids; not just on TV, but also online, in schools, and in stores. New guidelines being proposed are voluntary, and food companies can opt out. However, with four powerful agencies, including the FTC and the FDA, throwing their weight behind the proposal, the food industry is taking the measure seriously.
The guidelines are not directed only at kids younger than 12, but one of the most contentious issues is whether the marketing limits should be applied to older kids, aged 12 to 17. The deadline for public comments is July 14; the final guidelines are expected by the end of the year.
http://www.npr.org/2011/06/22/137245049/junk-food-fight-should-ads-stop-targeting-teens
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http://jama.ama-assn.org/content/305/24/2556.short
Be Vigilant for New-Onset Diabetes with High-Dose Statins,
Meta-Analysis Suggests
Compared with moderate-dose regimens, high-dose statins are associated with increased diabetes risk, according to a JAMA meta-analysis.
Researchers studied outcomes from five trials comparing high- versus moderate-dose statins in some 33,000 patients free of diabetes at baseline. During a mean follow-up of almost 5 years, the risk for new-onset diabetes was higher in the high-dose group (odds ratio, 1.12). The risk for cardiovascular events was, conversely, lower in the high-dose group (OR, 0.84). The authors estimate that 498 patients per year would need to take high-dose statins to cause one additional case of diabetes. To prevent one cardiovascular event, 155 patients would need to be treated.
Although the authors have not identified a mechanism for this effect, they "suggest that clinicians should be vigilant for the development of diabetes in patients receiving intensive statin therapy."
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Circulation 2011 May 24 ; 123:2292
Triglycerides and Cardiovascular Disease: The Experts Speak
Experts redefine an optimal triglyceride level and stress that lifestyle changes are required to reach it.
While debate continues about whether hypertriglyceridemia independently predicts coronary artery disease, mean triglyceride levels in the U.S. are rising, along with rates of obesity and diabetes. In a new scientific statement, the American Heart Association (AHA) outlines the scope of the problem and offers treatment recommendations. Triglyceride levels directly influence high- and low-density lipoprotein metabolism, and hypertriglyceridemia can be mediated genetically or acquired (e.g., in patients with hypothyroidism, diabetes, or renal disease).
The authors propose a "practical algorithm" for initial screening with nonfasting triglyceride measurement. If levels are <200 mg/dL (corresponding to <150 mg/dL on a fasting sample), they suggest that patients continue with healthy diet and activity levels. At levels ≥200 mg/dL, fasting lipoprotein measurement is advised, and suggested targets are provided for weight loss and intake of dietary carbohydrates, sugars, and fats. Increased physical activity and intake of 
-3 fatty acids also are advocated for their profound effects on elevated triglycerides levels. At the highest triglyceride levels or in symptomatic patients, pharmacologic therapy can be useful (e.g., to lower risk for pancreatitis in patients with triglycerides >500 mg/dL). At all triglyceride levels, the AHA recommends avoiding consumption of trans fats, which raise triglyceride levels and atherogenic lipid particles. Finally, the guidelines set <100 mg/dL as an optimal triglyceride level.
This statement summarizes what we know about triglycerides and their relation to disease and provides a framework for treating the many patients with suboptimal triglyceride levels. Patients should be advised that lifestyle changes in diet, weight loss, and exercise are basic to treating most cases of hypertriglyceridemia, although tightening the definition of an optimal triglyceride level inadvertently could invite additional prescribing.
— Kirsten E. Fleischmann, MD, MPH AN ADDITIONAL PERSPECTIVE FROM the Journal Watch general medicine EDITOR-in-chief:
In this AHA-sponsored statement, the authors acknowledge that the evidence for triglycerides as an independent predictor of cardiovascular events (i.e., after adjustment for other lipid fractions) remains controversial. They also acknowledge the lack of convincing clinical-trial evidence to support triglyceride-lowering drug therapies, independent of LDL-cholesterol–lowering or statin therapy; indeed, no benefit was seen in the recent AIM-HIGH study. Hence, this statement is somewhat self-contradictory: If drugs are not indicated (except to lower risk for pancreatitis when triglycerides are extremely elevated), and if lifestyle modifications that happen to lower triglycerides are worthwhile regardless of triglyceride levels, why should we closely monitor triglyceride levels? I am unaware of evidence that patients who track their triglyceride levels are more motivated to exercise, lose weight, and eat a heart-healthy diet than are patients who receive similar counseling without following triglycerides. A move to more-intense focus on triglyceride levels, and to a more stringent definition of "optimal" triglycerides, thus seems unnecessary and misguided.
— Allan S. Brett, MD Miller M et al. Triglycerides and cardiovascular disease: A scientific statement from the American Heart Association. Circulation 2011 May 24 ; 123:2292. (http://dx.doi.org/10.1161/CIR.0b013e3182160726)
http://www.ncbi.nlm.nih.gov/pubmed/21502576?dopt=Abstract
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FDA: Silicone Breast Implants Not 'Lifetime Devices'
Silicone breast implants are not "lifetime devices," the FDA said on Wednesday, noting that 20% of women who receive the implants for augmentation — and potentially half who receive them for reconstruction — will need to have them removed within 10 years.
The agency examined data from postapproval studies and from its own adverse event reporting system, and also conducted a literature review. It found that capsular contracture, reoperation, and implant removal were the most frequent adverse outcomes with silicone implants. Other common adverse events included implant rupture, wrinkling, asymmetry, scarring, pain, and infection. The longer the women had implants, the more likely they were to have complications.
The implants did not appear to cause breast cancer, reproductive problems, or connective tissue disease, although the FDA stressed that the data are preliminary.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm260235.htm
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Gut 2011 Jun; 60:814
Dogs Can Smell Cancer
A specially trained Labrador Retriever could detect colorectal cancer well, which lead to screening tests based on specific volatile organic compounds in breath and feces of patients.
Previous reports have suggested that dogs can detect skin, bladder, lung, breast, and ovarian cancers by scent. Now, using an 8-year-old female black Labrador Retriever from the St. Sugar Cancer Sniffing Dog Training Center in Chiba, Japan, researchers have evaluated a dog's ability to detect colorectal cancer (CRC).
Initially trained for water rescue, the dog began training for cancer detection in 2005, using breath samples from several hundred cancer patients and about 500 healthy volunteers. Each training session was complete when the dog could distinguish between samples from a cancer patient and four controls consecutively in dozens of trials. Correct sample identification was rewarded by play with a tennis ball. Before the present study, the dog could detect 12 types of cancer, including CRC.
The study involved breath samples from 33 CRC patients and 132 controls (volunteers with no history of cancer), as well as watery stool samples from 37 CRC patients and 148 controls. All the patients and controls had undergone colonoscopy, and about half the controls had colorectal polyps.
Compared with conventional colonoscopic diagnosis, the dog achieved a sensitivity and specificity of 91% and 99% with breath samples and 97% and 99% with watery stool samples. Accuracy was similar between early- and late-stage cancers.
Comment: The study authors note that the time and expense for educating a dog to detect cancers, the cost of a trainer, and inconsistencies in dogs' capacity to concentrate would render canine scent judgment impractical for CRC screening. However, the findings suggest the existence of CRC-specific volatile organic compounds. If such compounds can be identified, tests for their presence in breath or stool samples could evolve into tools for CRC screening.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology June 24, 2011
Citation(s):Sonoda H et al. Colorectal cancer screening with odour material by canine scent detection. Gut 2011 Jun; 60:814. http://www.ncbi.nlm.nih.gov/pubmed/21282130?dopt=Abstract
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Double CT Scans: Often Ordered, Rarely Needed
Thousands of Medicare patients undergo two computed tomography scans in the same day — and thus receive twice the radiation exposure — when only one scan is usually needed, according to a New York Times story published over the weekend.
Analysis of Medicare claims from 2008 revealed that over 200 hospitals performed double CT scans, one with iodine contrast and one without, for more than 30% of its Medicare chest patients — a number experts consider "far too high," the Times reports. Smaller community hospitals were more likely to administer double scans, sometimes for nearly 90% of patients, while larger teaching hospitals ordered them only rarely.
The national average was around 5%.
http://www.nytimes.com/2011/06/18/health/18radiation.html?_r=1
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Science 2011 May 31;
Retroviral Etiology for Chronic Fatigue Syndrome Questioned
New data challenge the association between a murine retrovirus and CFS — and the existence of the virus in the prostate cancer cell line from which it was first identified.
The report of an apparent link between a novel retrovirus (xenotropic murine leukemia virus–related virus; XMRV) and chronic fatigue syndrome (CFS) attracted much attention in 2009 (JW Infect Dis Oct 21 2009). However, multiple follow-up studies have yielded conflicting results (JW Infect Dis Sep 1 2010), and discoveries in two new studies challenge the validity of the original findings.
Seeking to confirm an association between XMRV and CFS, Knox and colleagues performed extensive virologic tests on blood samples from 61 CFS patients from the same clinical practice that provided the majority of participants covered in the 2009 report; 43 of them had been reported to be XMRV positive. Polymerase chain reaction (PCR) assays for nucleic acids derived from XMRV or murine leukemia viruses (MLVs) and assays for detecting infectious virus or virus-specific antibodies showed no evidence of XMRV or other MLVs in any of the patients. In addition, the researchers found that unheated human sera from either CFS patients or healthy controls readily inactivated XMRV and another tested MLV, and determined that MLV sequences contaminated 12 of 22 laboratory reagents used to detect such viruses.
Poprotka and colleagues sought to confirm the existence of XMRV by studying the human prostate cell line (CWR22Rv1) from which it was first identified. This cell line was derived from a primary human prostate tumor and underwent serial passage in nude mice. The researchers determined that XMRV was present in later passage xenografts but not in earlier ones. They screened multiple mouse strains and wild mice but did not detect endogenous XMRV in any of them. However, they did identify two murine proviruses (preXMRV-1 and preXMRV-2) that were present in host mice and could have recombined to produce XMRV during serial tumor passaging.
Comment: These findings strongly suggest that unrecognized laboratory contamination led to the initial findings on XMRV and CFS and highlight the pitfalls inherent in research methodologies involving nucleic acid amplification and sequencing, as well as the use of xenografts. Although questions remain about murine retroviruses and CFS, the possibility of a real association now seems remote. The editors of Science have issued an editorial expression of concern regarding the 2009 study.
— Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases June 22, 2011
Citation(s):Knox K et al. No evidence of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected. Science 2011 May 31; [e-pub ahead of print]. (http://dx.doi.org/10.1126/science.1204963)
Paprotka T et al. Recombinant origin of the retrovirus XMRV. Science 2011 May 31; [e-pub ahead of print]. (http://dx.doi.org/10.1126/science.1205292)
Alberts B. Editorial expression of concern. Science 2011 May 31; [e-pub ahead of print]. (http://dx.doi.org/10.1126/science.1208542)
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http://newsletter.vitalchoice.com/e_article002141255.cfm?x=bjDMlk1,b1h1R7NC
Fish Oil vs. Postpartum Depression
Clinical trial adds positive evidence to a mixed record; biology of omega-3s suggests they should support mothers’ mood
by Craig Weatherby
Depression is a risk for women during, and especially after pregnancy … a condition called postpartum depression. By some estimates, postpartum depression affects as many as one in four new mothers in the first year after childbirth. It can make a mother feel sad, worthless, and hopeless, and make it more difficult to care for and bond with her baby.
Back in 2007, an expert panel appointed by the American Psychiatric Association concluded that people who consume higher amounts of omega-3s from fish (EPA and DHA) generally enjoy reduced risks of depression and other mood disorders. For more on that, see “Top Psych Panel Says Omega-3s Deter Depression, Bipolar Disorder”.
But what about postpartum depression? Although most of the several epidemiological and clinical studies published to date produced positive evidence, the results are considered encouraging but inconclusive … in part because of the paucity of sound, reliable studies. As a researcher at Emory University put it in a review published in April of 2011, “The results are mixed, but one recently completed large trial found no evidence of benefit among women who received DHA during pregnancy.” (Ramakrishnan U 2011)
The authors of two other recent evidence reviews reached similar conclusions:
- “In conclusion, the question of whether EPA and DHA administration is effective in the prevention or treatment of perinatal depression cannot be answered yet. The quality of research in this area needs to improve.” (Jans LA et al. 2010)
- “Overall, results have been inconclusive, but further investigation of omega-3 fatty acids is warranted because they did improve depression scores and appeared to be safe during pregnancy.” (Borja-Hart NL, Marino J 2010)
(The perinatal period is the time immediately before and after birth … starting at about the 20th week of gestation and ending about one month after birth.) Recently, a small clinical trial from the University of Connecticut (UConn) found that omega-3 fish oil appears to reduce symptoms of postpartum depression, adding more pressure to conduct large, well-controlled trials. As the authors wrote, “These results offer a basis for guidelines for DHA consumption by pregnant women and for community-based efforts to increase awareness of the value of DHA/fish consumption for maternal mental health.” (Judge MP et al. 2011)
UConn study finds positive indications
For the past several years, Michelle Price Judge, an assistant professor-in-residence at the UConn School of Nursing, has been looking into how omega-3s derived from fish impact maternal and infant health. In a recent study, Judge focused on whether DHA – the omega-3 essential to brain development and function – lowers the risk of postpartum depression when it is consumed during pregnancy (Judge MP et al. 2011). Her coauthors included UConn Professor Cheryl Beck – an international expert on postpartum depression – and Carol Lammi-Keefe of Louisiana State University. They conducted a randomized, double-blind study involving 42 pregnant women, monitored from the 24th week of pregnancy to birth. The results were presented at Experimental Biology 2011 in Washington, D.C. in April. Dr. Judge’s team found that, compared with women who took a placebo pill, those who took 300mg of DHA five days a week had lower scores on a standardized postpartum depression screening scale (developed by Beck). The women in the fish oil group had significantly lower scores for symptoms of anxiety/insecurity, emotional liability (characterized by excessive emotional reactions and frequent mood changes), and “sense of loss of self”. However, because their study was quite small, Judge said that her group could not conclude that fish oil supplements reduce the risk or severity of major postpartum depression.
Omega-3s, fish fat, and pregnancy
In some animals, a deficiency of omega-3 DHA has been associated with lower brain levels of important neurotransmitters such as dopamine and serotonin, which play key roles in mood elevation. Additionally, high blood levels of omega-3s can reduce levels of certain messenger proteins “cytokines” that promote systemic inflammation, which also is considered a factor in depression.
Dr. Judge made these cogent comments:
“Generally, experts agree that the omega-3 fatty acids derived from fish are beneficial to maternal and infant health. Yet on average, pregnant women consume less than half of the level considered optimal during pregnancy. If women consume 12 ounces (two to three servings) of fish weekly, there is no need for fish oil supplementation. Women who consume very little or no fish should consider supplementation.” (UConn 2011)
Her opinion – that the rewards of fishy diets to children and pregnant/nursing mothers far outweighs any hypothetical risk – has ample support … see “Experts Urge an End to Fishy U.S. Advice for Mothers, Children” and “FDA Analysis Supports More Fish for Moms and Kids”. Worldwide, health authorities recommend that pregnant women consume at least 200 mg of DHA daily. In fact, experts recommend from 260mg to 660mg per day for all adult women, pregnant or otherwise. (See “How Much Sockeye Salmon Oil Should I Take?”.)
Fatty fish such as wild salmon, sardines, herring, tuna, including canned light tuna, are excellent sources of DHA and EPA … the omega-3 fatty acids found only in fish oil. Some fish, such as shark, swordfish, king mackerel, and marlin can contain high amounts of mercury, and should be avoided. Fish oil supplements provide a safe alternative, either because they have been chemically refined to remove almost all mercury, or because they come from naturally pure fish such as wild Alaskan salmon. Prior research has shown that the omega-3 fatty acids found in the primary fat of fish like salmon and tuna are preferentially transferred through the placenta during the later stages of pregnancy in order to help the baby grow and mature. As a result, expectant mothers often show a depletion of maternal stores of omega-3s in their bodies. According to Dr. Judge, this lack of DHA in mothers is compounded by the fact that pregnant women tend to eat only a fraction of the amount of fish and DHA considered optimal during pregnancy.
The research was funded by the Patrick and Catherine Weldon Donaghue Medical Research Foundation.
Sources: Borja-Hart NL, Marino J. Role of omega-3 Fatty acids for prevention or treatment of perinatal depression. Pharmacotherapy. 2010 Feb;30(2):210-6. Review. Freeman MP. Complementary and alternative medicine for perinatal depression. J Affect Disord. 2009 Jan;112(1-3):1-10. Epub 2008 Aug 8. Review.Jans LA, Giltay EJ, Van der Does AJ. The efficacy of n-3 fatty acids DHA and EPA (fish oil) for perinatal depression. Br J Nutr. 2010 Dec;104(11):1577-85. Epub 2010 Nov 16. Review.Judge MP et al. Maternal docosahexaenoic acid (DHA, 22:6n-3) consumption during pregnancy decreases postpartum depression (PPD) symptomatology. The FASEB Journal. 2011;25:349.7 Accessed at http://www.fasebj.org/cgi/content/meeting_abstract/25/1_MeetingAbstracts/349.7?sid=722a0ce8-35e9-4a7e-b5ae-625ef03534f3 Judge MP, Harel O, Lammi-Keefe CJ. A docosahexaenoic acid-functional food during pregnancy benefits infant visual acuity at four but not six months of age. Lipids. 2007 Mar;42(2):117-22. Epub 2007 Jan 19. Judge MP, Harel O, Lammi-Keefe CJ. Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 mo. Am J Clin Nutr. 2007 Jun;85(6):1572-7. Ramakrishnan U. Fatty acid status and maternal mental health. Matern Child Nutr. 2011 Apr;7 Suppl 2:99-111. doi: 10.1111/j.1740-8709.2011.00312.x. Review. University of Connecticut (UConn). Fish Oil May Reduce Postpartum Depression Symptoms. June 1, 2011. Accessed at http://today.uconn.edu/blog/2011/06/fish-oil-may-reduce-postpartum-depression-symptoms/
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J Dent Res 2011 Apr; 90:439
Bisphosphonate-Related Jaw Osteonecrosis — Back on the Radar Screen
Studies support a link between oral bisphosphonate use and jaw osteonecrosis, but absolute risk is very low.
Controversy about jaw osteonecrosis in oral bisphosphonate users was a hot topic several years ago (JW Gen Med Apr 8 2008), but it faded into the background when attention shifted to a possible connection between atypical femoral fractures and bisphosphonates (JW Womens Health May 4 2011). Now, two new NIH-funded studies, conducted in dental practice–based research networks, put the spotlight back on bisphosphonate-related osteonecrosis of the jaw (BRONJ).
In a case-control study that involved 119 dental practices in four U.S. metropolitan areas, 191 patients with BRONJ were compared with 573 control patients. About half the BRONJ patients had used oral bisphosphonates. In multivariate analysis, oral bisphosphonate use was strongly associated with BRONJ (odds ratio, 12.2).
In another retrospective study, researchers identified 23 BRONJ cases during roughly 10 years in two health maintenance organizations that provided dental benefits. Six BRONJ patients (26%) used oral bisphosphonates, compared with 4% of non-cases (adjusted OR for association between oral bisphosphonates and BRONJ, 15.5). The overall incidence of BRONJ was 0.63 cases per 100,000 person-years, but, among oral bisphosphonate users, it was 4.1 per 100,000 person-years.
Comment: BRONJ is recognized widely as a complication of high-dose intravenous bisphosphonate use for cancer treatment, but its association with oral use for osteoporosis is controversial. These observational studies have many limitations, but they suggest that oral use is a rare cause of BRONJ. Clinicians should keep this possibility in mind but should not let it deter use of bisphosphonates in osteoporotic patients who have evidence-based indications for these drugs.
— Allan S. Brett, MD Published in Journal Watch General Medicine May 5, 2011
Citation(s):Barasch A et al. Risk factors for osteonecrosis of the jaws: A case-control study from the CONDOR Dental PBRN. J Dent Res 2011 Apr; 90:439. (http://dx.doi.org/10.1177/0022034510397196) http://www.ncbi.nlm.nih.gov/pubmed/21317246?dopt=Abstract
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Circulation 2011 May 24; 123:2226
Even Short-Term NSAID Use Associated with Cardiovascular Events
Registry data show adverse effects of both selective cyclooxygenase-2 inhibitors and nonselective agents within the first week of treatment.
Since 2007, practice guidelines have advised clinicians about the risks of nonsteroidal anti-inflammatory drug (NSAID) use in patients with known cardiovascular disease or at high risk for ischemic heart disease. However, whether short-term NSAID use (e.g., for less than a week) can worsen outcomes in such patients is unclear. Therefore, investigators used data from the Danish National Patient Registry to assess the impact of NSAID use in >83,000 patients (mean age, 68; 63% men) after hospitalization for first myocardial infarction (MI) from 1997 through 2006.
More than 42% of the cohort received prescriptions for NSAIDs including ibuprofen (23%), diclofenac (13%), rofecoxib (5%), celecoxib (5%), and naproxen (2%). During follow-up, the primary outcome, a composite of death and recurrent MI, occurred in 42.1% of NSAID recipients. Compared with the overall study population, risk for a primary endpoint in NSAID recipients was significantly elevated in the first week of NSAID treatment (hazard ratio, 1.45), and the increase in risk remained significant throughout treatment (>90 days; HR, 1.55). In individual analysis, all NSAIDs except naproxen were associated with an increased risk for the primary outcome. Diclofenac conferred the highest risk, with a hazard ratio (3.26 in the first week of treatment) higher than that of rofecoxib, which was withdrawn from the U.S. market in 2004.
Comment: In this large, national study, NSAIDs — many of which are available without a prescription — were associated with a 45% increase in risk for recurrent MI or death within the first week of treatment in post-MI patients. When NSAID treatment was continued for 3 months, the increase in risk rose to 55%. It appears that no NSAID, no matter how short the duration of use, is without possible cardiovascular side effects in patients with coronary artery disease.
— JoAnne M. Foody, MD Published in Journal Watch Cardiology June 8, 2011
Citation(s): Schjerning Olsen A-M et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: A nationwide cohort study. Circulation 2011 May 24; 123:2226.
http://www.ncbi.nlm.nih.gov/pubmed/21555710?dopt=Abstract
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Ann Intern Med 2011 May 17; 154:656.
High-Selenium Yeast Supplements Improve Plasma Lipid Levels
But the effects of this treatment in individuals with normal or high baseline selenium concentrations remain unproven, as do clinical outcomes
Low selenium concentrations have been linked to increased cardiovascular mortality and morbidity. However, evidence supporting an association between selenium concentration and coronary heart disease risk is ambiguous. To find out more, investigators in the U.K. conducted a randomized, double-blind, parallel-group study involving 501 volunteers, aged 60 to 74, stratified by age and sex. Participants received high-selenium yeast at one of three doses (100, 200, or 300 µg/day) or placebo. At least one lipid measurement was available for 95% of participants at baseline, 6 months, or both.
At baseline, mean plasma selenium concentration was 91.2 µg/L, and higher selenium concentrations were correlated with higher total cholesterol and HDL levels and with lower total cholesterol-to-HDL ratios. During 6-month follow-up, plasma selenium increased significantly in all three selenium groups but remained unchanged in the placebo group. Selenium supplementation at both 100 µg/day and 200 µg/day significantly reduced mean total cholesterol and non-HDL levels. The 300 µg/day dose had no significant effect on total cholesterol or non-HDL levels but significantly increased mean HDL levels. No major adverse events were reported.
Comment: Selenium supplementation produced modest improvements in plasma lipids in this cohort; however, the mean baseline selenium concentration was low compared with the mean selenium concentration in the U.S., recently reported to be 136.7 µg/L. Although the findings are statistically significant, their clinical significance is unclear. Selenium supplementation as adjunct or alternative therapy for hyperlipidemia is therefore unjustified in the absence of low serum selenium levels, which is rare in the U.S.
— Joel M. Gore, MD Published in Journal Watch Cardiology June 1, 2011
Citation(s):Rayman MP et al. Effect of supplementation with high-selenium yeast on plasma lipids: A randomized trial. Ann Intern Med 2011 May 17; 154:656. http://www.ncbi.nlm.nih.gov/pubmed/21576533?dopt=Abstract
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Ann Intern Med 2011 May 17; 154:656
High-Selenium Yeast Supplementation Doesn't Lower Plasma Lipid Levels
Selenium supplementation should not be recommended.
Studies have suggested that selenoproteins inhibit oxidation of lipids and platelet aggregation and reduce inflammation. However, results of studies in which researchers evaluated the relation between selenium and lipids have been somewhat contradictory. To determine whether selenium supplementation modifies serum lipid levels, U.K. researchers randomized nearly 500 people (age range, 60–74) to daily placebo or selenium (100, 200, or 300 µg), given in the form of high-selenium yeast.
At 6 months, people who received selenium at the 100-µg or 200-µg doses had modest mean reductions from baseline in total cholesterol levels (–8.5 mg/dL and –9.7 mg/dL, respectively); no improvement was noted with the 300-µg dose. No significant changes in HDL cholesterol levels were observed in those receiving 100-µg or 200-µg doses of selenium; among people in the 300-µg group, mean HDL cholesterol levels rose 2.3 mg/dL.
Comment: In this randomized trial, high-selenium yeast supplementation failed to improve lipid levels in a clinically meaningful way. As the authors note, selenium supplementation should not be recommended to patients.
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine June 16, 2011
Citation(s):Rayman MP et al. Effect of supplementation with high-selenium yeast on plasma lipids: A randomized trial. Ann Intern Med 2011 May 17; 154:656. (http://www.annals.org/content/154/10/656.full)
http://www.ncbi.nlm.nih.gov/pubmed/21576533?dopt=Abstract
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Lancet 2011 Jun 9
Simvastatin plus Ezetimibe Improves Cardiovascular Outcomes in Patients with Chronic Kidney Disease
But would a statin alone have produced similar results?
Two previous trials failed to demonstrate the effectiveness of statins for preventing adverse cardiovascular events in patients on dialysis (JW Cardiol Aug 19 2005 and Mar 30 2009). In SHARP, a randomized trial, investigators compared simvastatin plus ezetimibe with placebo. Of the 9270 patients (age, ≥40; mean age, 62; 63% men) with chronic kidney disease and no histories of acute myocardial infarction (AMI) or coronary revascularization, about one third were on dialysis. The study was funded by the drug combination's manufacturer, who participated in the study design.
Patients had creatinine levels of at least 1.7 mg/dL in men or 1.5 mg/dL in women. Nonadherent participants were excluded after a 6-week, single-blind, run-in placebo course. The primary endpoint was first major atherosclerotic event. At baseline, mean total cholesterol level was 189 mg/dL, and mean LDL cholesterol level was 108 mg/dL.
At study midpoint, the mean LDL cholesterol level was 33 mg/dL lower in the treatment group than in the placebo group. During a median follow-up of 4.9 years, a primary endpoint occurred in 11.3% of patients in the treatment group and 13.4% of those in the placebo group (relative risk, 0.83; 95% confidence interval, 0.74–0.94; P=0.002). Although the rate of nonfatal AMI or death from coronary heart disease did not differ significantly between groups, the rates of nonhemorrhagic stroke and revascularization (coronary, carotid, aortic, or leg) were significantly lower in the treatment group, whereas all-cause mortality was nonsignificantly higher (24.6%, vs. 24.1% with placebo). The study was underpowered for comparison by dialysis status; the rate of the primary endpoint in patients on hemodialysis was 15.2% in the treatment group and 15.9% in the placebo group.
Comment: This study is difficult to translate into practice for several reasons. First, it is underpowered to show whether combination therapy improves outcomes in patients on hemodialysis, the group that did not benefit in previous statin studies. Second, the investigators did not compare the drug combination to statin-only therapy, so we cannot determine whether ezetimibe conferred any additional benefit over statin therapy alone. Finally, although the statin and ezetimibe combination was efficacious in this cohort, it primarily affected revascularization — a soft endpoint — rather than death or adverse cardiac events. The bottom line: Our approach to patient care will be the same today as it was before SHARP's publication.
— Harlan M. Krumholz, MD, SM and Allan S. Brett, MD Published in Journal Watch General Medicine June 9, 2011
Citation(s):Baigent C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): A randomised placebo-controlled trial. Lancet 2011 Jun 9; [e-pub ahead of print]. (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960739-3/abstract)
Stevens KK and Jardine AG. SHARP: A stab in the right direction in chronic kidney disease. Lancet 2011 Jun 9; [e-pub ahead of print]. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960822-2/fulltext
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Am J Clin Nutr 2011 Jun; 93:1196.
Playing Video Games Increases Caloric Intake
A 1-hour session increased caloric intake but not hunger in adolescent boys.
To examine whether video game playing contributes to obesity by increasing caloric intake, investigators conducted an experimental study under laboratory conditions in 22 healthy, normal-weight male adolescents (age range, 15–19 years) in Denmark, with each subject serving as his own control.
Investigators served participants a breakfast that provided 25% of their estimated daily energy requirement and then randomized them to either rest in a chair or play a soccer video game for 1 hour. Participants were served a pasta lunch and asked to eat until satiated. Blood specimens for serum glucose, insulin, cortisol, and ghrelin were obtained every 10 minutes, and indirect calorimetry was used to estimate caloric expenditure. Participants completed visual analog scales to assess hunger, satiety, and food preferences and a dietary log to record caloric intake for the remainder of the day. The experiment was repeated 1 to 4 weeks later with each participant assigned to the other condition.
On average, participants expended 21 kcal more when playing video games than when resting. Mean serum glucose levels were significantly higher during video game playing than during rest, but, otherwise, hormone levels were similar during the two conditions. Although no significant differences in subjective appetite sensations, hunger, or food preferences were reported between rest and video game sessions, participants consumed 80 kcal more at lunch and 104 kcal more during the remainder of the day on video game days — far more than the calories expended while playing video games.
Comment: Unfortunately, these investigators did not study girls, and we do not know whether the same results would be obtained outside laboratory settings or with newer video game systems that require players to be more active. The authors posit that the stress of playing video games interferes with satiety signals or activates the stress-reward system, leading to increased caloric intake. Regardless, we now have more evidence to support counseling parents to limit video game playing. Encouraging teenagers to consume healthy snacks rather than calorically dense but nutritionally empty ones might also mitigate the effect of post–video game grazing.
— Alain Joffe, MD, MPH, FAAP Published in Journal Watch Pediatrics and Adolescent Medicine June 22, 2011
Citation(s):Chaput JP et al. Video game playing increases food intake in adolescents: A randomized crossover study. Am J Clin Nutr 2011 Jun; 93:1196.
http://www.ncbi.nlm.nih.gov/pubmed/21490141?dopt=Abstract
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